LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial.

Background: Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited.

Methods: The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions.

Discussion: LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients.

Trial Registration: ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021.